Patients were stratified by type of operation, nodal stage, T stage and time from surgery to registration.

Arm 1 patients received 2 five day cycles of bolus 5-FU before and after XRT (50.4 - 54Gy) plus PVI 5-FU during XRT. Arm 2 patients received PVI 5-FU 42 days before, during and 56 days after XRT. Arm 3 patients received 2 five day cycles of bolus 5-FU with leucovorin before and after XRT and bolus 5-FU/leucovorin during XRT. Lev was also given before and after XRT in this arm.

Results

Toxicity was similar with 1% lethal toxicity in all arms. However, Grade III/IV hematologic toxicity was about 50% in the two bolus arms vs 4% in the all PVI arm.

RFS and OS was similar in all arms with 3 year OS of 81-83%.

However when comparing arm 1 only to arm 2, 5 year OS was 67% vs 72% (one sided p=0.04) with the trend favoring all PVI 5-FU.

Author's Conclusions

A nonsignificant trend towards improved OS with all PVI 5-FU was seen. This deserves further investigation but is not sufficient to make this regimen the standard.

Bolus regimens with no PVI are effective and especially useful if a central line needs to be avoided.

Further study is needed to determine if the added toxicity and cost of PVI drug delivery is justified by the potential clinical benefit.

Clinical/Scientific Implications

This study provides evidence that there is no dramatic difference in efficacy between different administration schedules of 5-FU for adjuvant rectal cancer treatment. This provides flexibility for the clinician to choose a regimen based on factors such as desired toxicity profile, demands of the patient and ability to place a central line. Further prospective studies of PVI 5-FU vs bolus are needed in order to determine if the non-significant trend towards improved OS with PVI seen in this study truly exists. For the moment any of these regimens are acceptable in clinical practice.